This proposal addresses the physiological significance of the ovarian insulin-like growth factor (IGF) system and the more general phenomenon of ligand targeting in autocrine/paracrine systems. Information from this laboratory and others suggests that the ovarian IGF system serves as a local amplification mechanism for gonadotropin effects and that it may participate in ovarian follicle selection. To understand and control this system, we require more detailed information about the hormonal regulation of IGF-I secretion, the processing of IGF-I, and its targeting for autocrine, paracrine, or endocrine effects. The complex family of IGF binding proteins (IGFBPs) which are abundantly expressed in the ovary, seem critical to these processes. To establish the importance of these components and their interaction, we will use well-characterized granulosa and theca cell cultures which express and respond to IGFs and IGFBPs. The hormonal regulation of their secretion and the nature of the processed secretory products will be established. Particular emphasis will be placed on transcriptional effects of gonadotropins, growth hormone, gonadal steroids and other ovarian growth factors. To determine the relevance of these phenomena to ovarian physiology in vivo, the expression of these key regulatory proteins will be examined in a well-characterized porcine model of ovarian follicular development. Finally, to demonstrate unequivocally the importance of these proteins in ovarian cell function, we will enhance, diminish, and/or qualitatively alter their expression in cell culture with anti-sense oligonucleotides and transfected expression vectors which have been constructed to enhance or inhibit the secretion of IGF-I and IGFBPs. Collectively, these experiments should provide more detailed information about this system than is currently available in any autocrine system. Enhancement of human fertility through stimulation of the ovarian IGFs has already been demonstrated. Accordingly, the information and techniques developed in these studies may have wide applications in health and reproduction.